Prostaglandin E2 (abbreviated as PGE2) has been known as a metabolite in the arachidonic acid cascade. It has been known that PGE2 possesses cyto-protective activity, uterine contractile activity, a pain-inducing effect, a promoting effect on digestive peristalsis, an awaking effect, a suppressive effect on gastric acid secretion, hypotensive activity, and diuretic activity.
In the recent study, it was found hat PGE2 receptor was divided into some subtypes which possesses different physical roles from each other. At present, four receptor subtypes are known and they are called EP1, EP2, EP3 and EP4 (Negishi M. et al, J. Lipid Mediators Cell Signaling 12, 379–391 (1995)) respectively.
Among these subtypes, EP4 receptor was believed to be involved in suppression of TNF-α production and induction of IL-10 production. So the compounds which can bind to EP4 receptor strongly and show the antagonizing activity, are useful for the prevention and/or treatment of diseases including bone diseases (such as osteoporosis, rheumatoid arthritis, osteoarthritis, abnormal bone formation etc.) and cancer (formation, proliferation, metastasis to organs, and to bones, hypercalcemia etc. and systemic granuloma, immunological diseases such as ALS, multiple sclerosis, Sjoegren's syndrome, systemic lupus erythematosus, AIDS etc. and allergy (conjunctivitis, rhinitis, contact dermatitis, psoriasis), atopic dermatitis, asthma, pyorrhea, gingivitis, periodontitis, neuronal cell death, Alzheimer's disease, pulmonary injury, hepatopathy, acute hepatopathy, nephritis, renal failure, myocardiac ischemia, Kawasaki disease, scald, ulcerative colitis, Crohn's disease, multiple organ failure etc. Moreover, EP4 is thought to be involved in sleeping disorders and platelet aggregation, so the compounds are considered to be useful.
On the other hand, in the specification of JP-A-51-115456, as a compound analogous to the compound of the present invention, 2-[2-(benzoylamino)phenylmethyl]benzoic acid is disclosed as a synthetic example. This application is only to disclose the process for the synthesis and nothing is described about pharmacological effect etc.